As a means for delivering a pharmaceutical agent to the intestine without the agent disintegrating in the stomach, a method has been known of applying an enteric coating onto a coating film (i.e. onto the shell) of a hard capsule.
Recently, a hard capsule in which the film (outer shell film) itself of the hard capsule is acid-resistant has been developed and sold (for example, “DRCAPS™” from Capsugel). Such hard capsules are superior in that a further enteric coating does not necessarily have to be applied onto the coating film (outer shell) of the capsule.
These kinds of hard capsules having acid resistance are useful because the shell does not normally dissolve even in an acidic solution having a pH of 1.2 (in other words, because the hard capsule does not disintegrate in the stomach of a living organism). In particular, when filling a hard capsule with a substance such as a pharmaceutical agent or the like for which no problems would occur as long as the hard capsule does not disintegrate in the stomach (for example, garlic and the like which may cause a return smell), the anticipated effects can be achieved with no remarkable problems.
However, upon careful examination of hard capsule formulations, including hard capsules with acid resistance that do not achieve sufficient effects, the present inventors made the surprising discovery that even if the hard capsule does not disintegrate in the stomach, gastric acid may gradually penetrate through the hard capsule outer shell over time because the shell itself of the hard capsule is not waterproof. As a result, the present inventors discovered that, since a substance such as a pharmaceutical agent or the like that is filled within a hard capsule makes contact with an acid (gastric acid), the anticipated effects cannot be achieved when filling a hard capsule with a substance such as a pharmaceutical agent or the like (for example, proteins (royal jelly, milk proteins, etc.), enzymes (nattokinase (source Bacillus subtilis var.natto), coenzymes, etc.), and viable bacteria (lactic acid bacteria, bifidobacteria, etc.) whose components deteriorate (change, decompose, or die) upon contact with an acid.
WO 2007/098612 A1 relates to gelatin compositions with covalent attachments forming functionalized gelatin.
U.S. Pat. No. 5,849,327 relates to pharmaceutical compositions with polymeric beads and polysaccharides, where the dosage form has an enteric coating.
United States Patent Application, Publication No. 2012/0288562 A1 assigned to Capsugel Belgium NV relates to acid resistant capsules.